Detection of cancer by elevated levels of bcl-2

Abstract

The present invention relates to a method for the diagnosis, prognosis, and monitoring of cancer, such as early or late stage ovarian cancer, in a subject by detecting Bcl-2 in a biological sample from the subject, preferably a urine or blood sample. Bcl-2 may be measured using an agent that detects or binds to Bcl-2 protein or an agent that detects or binds to encoding nucleic acids, such as antibodies specifically reactive with Bcl-2 protein or a portion thereof. The invention further relates to kits for carrying out the methods of the invention. The invention further relates to a device for the rapid detection of Bcl-2 in a bodily fluid and methods for rapidly measuring Bcl-2 in a bodily fluid.

I claim: 
     
       1. A method for determining whether a Bcl-2 protein level in a urine sample from a subject is at, above, or below a threshold level, the method comprising:
 (a) obtaining the urine sample from the subject; 
 (b) contacting the urine sample with a device comprising:
 i) an application zone for receiving a urine sample; 
 ii) a labeling zone containing a monoclonal or polyclonal antibody that binds to Bcl-2 protein in the sample; and 
 iii) a detection zone where Bcl-2 protein-bound monoclonal or polyclonal antibody is retained to give a signal that indicates that Bcl-2 protein level in the urine sample is lower than the threshold level and to give a different signal that indicates that Bcl-2 protein level in the urine sample is at or above the threshold level, wherein the threshold level is 1.8 ng/ml; 
 and 
 
 (c) detecting a signal from the detection zone of the device to determine whether the Bcl-2 protein level in the urine sample is at, above, or below the threshold level. 
 
     
     
       2. The method of  claim 1 , wherein the labeling zone contains a monoclonal antibody that binds to Bcl-2 protein. 
     
     
       3. The method of  claim 1 , wherein said detecting of (b) further comprises linking or incorporating a label onto the monoclonal or polyclonal antibody. 
     
     
       4. The method of  claim 1 , wherein the device comprises the monoclonal or polyclonal antibody that binds to Bcl-2 protein at a concentration such that:
 i) when the sample contains 1.8 ng/ml Bcl-2, half of the monoclonal or polyclonal antibodies bind to Bcl-2 in the sample and half of the monoclonal or polyclonal antibodies do not bind to Bcl-2; 
 ii) when the sample contains less than 1.8 ng/ml Bcl-2, less than half of the monoclonal or polyclonal antibodies bind to Bcl-2 in the sample and more than half of the monoclonal or polyclonal antibodies do not bind to Bcl-2; and 
 iii) when the sample contains more than 1.8 ng/ml Bcl-2, more than half of the monoclonal or polyclonal antibodies bind to Bcl-2 in the sample and less than half of the monoclonal or polyclonal antibodies do not bind to Bcl-2. 
 
     
     
       5. The method of  claim 1 , further comprising, before, during, and/or after detection of Bcl-2 is carried out, detecting one or more additional markers in a biological sample obtained from the subject. 
     
     
       6. The method of  claim 5 , comprising detecting one or more additional markers selected from CA125, LPA, and OVXI in the biological sample obtained from the subject. 
     
     
       7. The method of  claim 6 , wherein the biological sample is a blood sample. 
     
     
       8. The method of  claim 7 , wherein the additional biomarker is CA125 and the method comprises determining whether a CA125 protein level in the blood sample obtained from the subject is at, above, or below a second threshold level. 
     
     
       9. The method of  claim 8 , wherein the second threshold level is 35 U/ml. 
     
     
       10. A method for determining whether a Bcl-2 protein level in a urine sample from a subject is at, above, or below a threshold level, the method comprising:
 (a) obtaining the urine sample from the subject; 
 (b) contacting the urine sample with a device comprising:
 i) an application zone for receiving a urine sample; 
 ii) a labeling zone containing a monoclonal or polyclonal antibody that binds to Bcl-2 protein in the sample; and 
 iii) a detection zone where Bcl-2 protein-bound monoclonal or polyclonal antibody is retained to give a signal that indicates that Bcl-2 protein level in the urine sample is lower than the threshold level and to give a different signal that indicates that Bcl-2 protein level in the urine sample is at or above the threshold level, wherein the threshold level is 1.8 ng/ml; and 
 
 (c) detecting a signal from the detection zone of the device to determine whether the Bcl-2 protein level in the urine sample is at, above, or below the threshold level; 
 wherein, the device comprises the monoclonal or polyclonal antibody that binds to Bcl-2 protein at a concentration such that: 
 i) when the sample contains 1.8 ng/ml Bcl-2, half of the monoclonal or polyclonal antibodies bind to Bcl-2 in the sample and half of the monoclonal or polyclonal antibodies do not bind to Bcl-2; 
 ii) when the sample contains less than 1.8 ng/ml Bcl-2, less than half of the monoclonal or polyclonal antibodies bind to Bcl-2 in the sample and more than half of the monoclonal or polyclonal antibodies do not bind to Bcl-2; and 
 iii) when the sample contains more than 1.8 ng/ml Bcl-2, more than half of the monoclonal or polyclonal antibodies bind to Bcl-2 in the sample and less than half of the monoclonal or polyclonal antibodies do not bind to Bcl-2. 
 
     
     
       11. The method of  claim 10 , wherein less than half the monoclonal or polyclonal antibodies that bind to Bcl-2 protein in the sample give the signal that indicates that Bcl-2 protein level in the urine sample is below 1.8 ng/ml and half or more than half of the monoclonal or polyclonal antibodies that bind to Bcl-2 protein in the sample give the different signal that indicates that Bcl-2 protein level in the urine sample is at or above 1.8 ng/ml.